The sensory shark: high-quality morphological, genomic and transcriptomic data for the small-spotted catshark Scyliorhinus canicula reveal the molecular bases of sensory organ evolution in jawed vertebrates.

Cartilaginous fishes (chimaeras and elasmobranchs -sharks, skates and rays) hold a key phylogenetic position to explore the origin and diversifications of jawed vertebrates. Here, we report and integrate reference genomic, transcriptomic and morphological data in the small-spotted catshark Scyliorhinus canicula to shed light on the evolution of sensory organs. We first characterise general aspects of the catshark genome, confirming the high conservation of genome organisation across cartilaginous fishes, and investigate population genomic signatures. Taking advantage of a dense sampling of transcriptomic data, we also identify gene signatures for all major organs, including chondrichthyan specializations, and evaluate expression diversifications between paralogs within major gene families involved in sensory functions. Finally, we combine these data with 3D synchrotron imaging and in situ gene expression analyses to explore chondrichthyan-specific traits and more general evolutionary trends of sensory systems. This approach brings to light, among others, novel markers of the ampullae of Lorenzini electro-sensory cells, a duplication hotspot for crystallin genes conserved in jawed vertebrates, and a new metazoan clade of the Transient-receptor potential (TRP) family. These resources and results, obtained in an experimentally tractable chondrichthyan model, open new avenues to integrate multiomics analyses for the study of elasmobranchs and jawed vertebrates.

The role of motivation on physical activity and screen time behaviors among parent-adolescent dyads: The FLASHE study.

Behavioral theories inform the development of lifestyle interventions to address low participation in physical activity (PA); however, relatively little is known about the value of self-determination theory (SDT) for explaining screen time (ST) behaviors or in extending SDT into a dyadic context. Actor-partner (i.e., parent-adolescent) interdependence models (APIMs) allow for examination of these interpersonal relationships. The purpose of this study was to examine PA and ST among parent-adolescent dyads using the cross-sectional Family Life, Activity, Sun, Health, and Eating (FLASHE) Study. Parent-adolescent dyads provided responses to online surveys addressing PA (n = 1177 dyads) and ST (n = 1489 dyads) behaviors. We examined the influence of SDT-based constructs (perceived competence and motivation) on PA and ST behaviors. Structural equations were used to estimate APIMs in STATA 15.1. Full models provided a good fit to the data. For both PA and ST, perceived competence was more strongly associated with motivation among adolescents compared with parents (PA: ß = 0.72 vs. 0.58, ST: ß = 0.34 vs. 0.22, p's < 0.001). Parental motivation was associated with parental PA and both adolescent motivation for PA and ST (p's < 0.001). Parental motivation was not associated with adolescent ST-behavior. Adolescent motivation was only associated with parent motivation for PA. In the FLASHE study, SDT constructs extend acceptably to the dyadic setting, with PA models providing a slightly better fit to the data than ST models. Longitudinal studies that target perceived competence and the self-regulation of motivation in parents and their adolescents are a next logical step to understanding both PA and ST behaviors.

Healthy Body, Healthy Mind: A Mindset Intervention for Obese Youth.

As growth mindset intervention research continues to develop, more work is needed to understand how to most effectively implement these interventions to encourage healthy cognitions and behaviors. The present study details the initial testing of a single-session, online mindset intervention (Healthy Body, Healthy Mind) for obese children and adolescents enrolled in obesity treatment clinics. Using a pre to post-test design, results indicated that growth mindsets of health and cognitions related to health behavior (nutrition and exercise self-efficacy and perceived control) increased significantly. However, despite efforts to mitigate feelings of culpability, blame also increased from pretest to post-test. Yet, body dissatisfaction decreased significantly. Intrinsic value for health behaviors remained unchanged from pretest to post-test. Analysis of narratives suggests that youth were engaged with the intervention content. Additionally, when youth's narratives incorporated themes related to the changeable nature of the attribute, they also self-reported stronger growth mindsets. In the discussion, we note implications of findings for the development of large-scale health-based growth mindset interventions that are developmentally-appropriate for children and adolescents.

Influence of Temperature and Precipitation Anomaly on the Seasonal Emergence of Invasive Bark Beetles in Subtropical South America.

Several invasive bark beetle species have caused major economic and ecological losses in South America. Accurate predictions of beetle emergence times will make control efforts more efficient and effective. To determine whether bark beetle emergence can be predicted by season, temperature, or precipitation, we analyzed trapping records for three introduced pest species of bark beetles in Uruguay. We used trigonometric functions as seasonal predictors in generalized linear models to account for purely seasonal effects, while testing for effects of temperature and precipitation. Results show that all three beetle species had strong but unique seasonal emergence patterns and responded differently to temperature and precipitation. Cyrtogenius luteus (Blandford) emerged in summer and increased with precipitation but was not affected by temperature. Hylurgus ligniperda (Fabricius) emerged in winter and increased with temperature but was not affected by precipitation. Orthotomicus erosus (Wollaston) had a primary emergence in spring, and a smaller emergence in early summer, but showed no significant relationship with temperature or precipitation. This study shows that the emergence of these bark beetle species in Uruguay is influenced by seasonality more than by temperature and precipitation fluctuations. It also shows how seasonality can be easily incorporated into models to make more accurate predictions about pest population dynamics.

Intensity-modulated Radiotherapy for Anal Cancer: Dose-Volume Relationship of Acute Gastrointestinal Toxicity and Disease Outcomes.

AIMS: Intensity-modulated radiotherapy (IMRT) is increasingly used in the treatment delivery of chemoradiotherapy in anal cancer with the ability to reduce toxicity. We report on 4 year outcomes since the introduction of IMRT and identify the most predictive bowel organ at risk that correlates with acute diarrhoea. MATERIALS AND METHODS: Fifty-eight patients receiving definitive chemoradiotherapy for squamous or basaloid cell anal carcinoma (T1-4NanyM0) were reviewed. Fifty-four per cent of patients had stage III disease and most (79%) were treated with a dose of 54 Gy in 30 fractions. Patient acute gastrointestinal toxicity was recorded using Common Terminology Criteria of Adverse Events (CTCAE) diarrhoea grading. Four different methods of bowel were re-contoured for each patient and correlated with acute diarrhoea. Locoregional control and overall survival were analysed. RESULTS: CTCAE grade 3 or more diarrhoea occurred in 11/58 patients (19%). Seven patients did not complete treatment; 10 patients (17%) required a treatment break of 3 or more days. 'Bowel cavity' was the best predictor of acute grade 3 toxicity using volume (P = 0.002) or volume to bowel cavity in 5 Gy bins (V5-V50Gy); P < 0.05. Bowel cavity V30Gy ≤ 300 cm3 predicts a 6% grade 3 diarrhoea risk versus > 300 cm3 predicts a 42% risk. Four year progression-free survival was 84% (95% confidence interval 73-92%) and overall survival was 88% (95% confidence interval 75-95%). CONCLUSION: Chemoradiation using IMRT provides excellent local control and acceptable acute gastrointestinal toxicity. Bowel cavity is the most sensitive predictor for grade 3 versus grade 0-2 diarrhoea, with any volume receiving 5-50 Gy discriminatory.

3D microfluidic liver cultures as a physiological preclinical tool for hepatitis B virus infection.

With more than 240 million people infected, hepatitis B virus (HBV) is a major health concern. The inability to mimic the complexity of the liver using cell lines and regular primary human hepatocyte (PHH) cultures pose significant limitations for studying host/pathogen interactions. Here, we describe a 3D microfluidic PHH system permissive to HBV infection, which can be maintained for at least 40 days. This system enables the recapitulation of all steps of the HBV life cycle, including the replication of patient-derived HBV and the maintenance of HBV cccDNA. We show that innate immune and cytokine responses following infection with HBV mimic those observed in HBV-infected patients, thus allowing the dissection of pathways important for immune evasion and validation of biomarkers. Additionally, we demonstrate that the co-culture of PHH with other non-parenchymal cells enables the identification of the cellular origin of immune effectors, thus providing a valuable preclinical platform for HBV research.

T cell immunity to Zika virus targets immunodominant epitopes that show cross-reactivity with other Flaviviruses.

Zika virus (ZIKV) Infection has several outcomes from asymptomatic exposure to rash, conjunctivitis, Guillain-Barré syndrome or congenital Zika syndrome. Analysis of ZIKV immunity is confounded by the fact that several related Flaviviruses infect humans, including Dengue virus 1-4, West Nile virus and Yellow Fever virus. HLA class II restricted T cell cross-reactivity between ZIKV and other Flaviviruses infection(s) or vaccination may contribute to protection or to enhanced immunopathology. We mapped immunodominant, HLA class II restricted, CD4 epitopes from ZIKV Envelope (Env), and Non-structural (NS) NS1, NS3 and NS5 antigens in HLA class II transgenic mice. In several cases, ZIKV primed CD4 cells responded to homologous sequences from other viruses, including DENV1-4, WNV or YFV. However, cross-reactive responses could confer immune deviation - the response to the Env DENV4 p1 epitope in HLA-DR1 resulted in IL-17A immunity, often associated with exacerbated immunopathogenesis. This conservation of recognition across Flaviviruses, may encompass protective and/or pathogenic components and poses challenges to characterization of ZIKV protective immunity.

Physical activity and family-based obesity treatment: a review of expert recommendations on physical activity in youth.

Targeting physical inactivity in children is pertinent to aiding in the decrease of childhood obesity rates. Only 33% of adolescents are obtaining the recommended goal of at least 60 min of physical activity per day. The objectives of this review are to summarize professional recommendations for physical activity and exercise in children and adolescents, and identify family-centred strategies that can be implemented by weight management clinicians. Clinically oriented recommendations and policy statements from professional organizations were identified through literature and internet searches, summarized using rubrics of aerobic, muscle strengthening and bone strengthening exercise, then examined for details on family-based focus, inclusion of child developmental stage and age, and application to the prevention and treatment of obesity. Current recommendations give guidelines for the amount of physical activity that children should acquire and how many days a week activities should occur. However, available guidelines need an improved approach to addressing the role of the parents and caregivers in targeting physical activity and weight management in youth. Efforts must be taken in order to make sure that the types of physical activity offered are both suitable and enjoyable. Sports, games, free play and other age appropriate activities are adequate ways to increase moderate to vigorous physical activity in children. Differentiating physical activities types in accordance with developmental stage, level of enjoyment, and family characteristics is needed to establish sustainable habits. One paediatric obesity program has developed approaches to teaching families fun and engaging ways to be active together.

A rapidly-reversible absorptive and emissive vapochromic Pt(II) pincer-based chemical sensor.

Selective, robust and cost-effective chemical sensors for detecting small volatile-organic compounds (VOCs) have widespread applications in industry, healthcare and environmental monitoring. Here we design a Pt(II) pincer-type material with selective absorptive and emissive responses to methanol and water. The yellow anhydrous form converts reversibly on a subsecond timescale to a red hydrate in the presence of parts-per-thousand levels of atmospheric water vapour. Exposure to methanol induces a similarly-rapid and reversible colour change to a blue methanol solvate. Stable smart coatings on glass demonstrate robust switching over 104 cycles, and flexible microporous polymer membranes incorporating microcrystals of the complex show identical vapochromic behaviour. The rapid vapochromic response can be rationalised from the crystal structure, and in combination with quantum-chemical modelling, we provide a complete microscopic picture of the switching mechanism. We discuss how this multiscale design approach can be used to obtain new compounds with tailored VOC selectivity and spectral responses.

Satisfaction and attrition in paediatric weight management.

Paediatric obesity treatment experiences unacceptably high rates of attrition. Few studies have explored parent and child perspectives on dropout. This study sought to capture child and parent experience in treatment and expressed contributors to attrition. Children and parents enrolled in a single family-based weight management programme participated in semi-structured interviews, conducted either upon completion of the first intensive phase of treatment or program dropout. Interviews were recorded, transcribed and coded using a multistage inductive approach. Interviews were obtained from 57 parents and 30 children, nearly equal between 'completers' or 'dropouts'. Five themes emerged: overall positive experience with programme; logistical challenges of participation; improved health; discrepancies between child and parent experience and perception, and importance of structure and expectations of weight loss. Primary reasons given for dropout were time commitment; distance from clinic; missed school and work; lack of dedicated adolescent programme; clinic hours; and stress. Few parents or children expressed dissatisfaction. Children reportedly enjoyed 'having someone to talk to' about weight, and spending increased time with family. Children and parents overall reported positive experiences in this weight management programme. Attrition appears more related to logistical issues than low satisfaction. Innovative approaches to help overcome logistical challenges and preserve positive aspects may help in decreasing programme attrition.

Pes planus and paediatric obesity: a systematic review of the literature.

Children with obesity report musculoskeletal pain more than normal-weight children; this may be linked with literature suggesting children with obesity have higher prevalence of pes planus (flatfoot). To further elucidate whether this relation occurs, we conducted a systematic literature review on the co-occurrence of pes planus and paediatric obesity. Empirical articles published until September 2013 were obtained through an electronic search of MEDLINE and SPORTDiscus; included articles examined the association between body weight and pes planus in children. Thirteen cross-sectional studies of varied designs were identified. Methods used to diagnose pes planus varied between studies: imaging modalities, anthropometric measurements and clinical examination. Across all studies, pes planus prevalence among children with obesity ranged widely from 14 to 67%. Nearly all studies indicated increasing pes planus in children with increasing weight. No studies evaluated pain/complications related to pes planus. Our review suggests increased prevalence of pes planus among children with obesity or increasing weight status. Because of differing methodologies, lack of consensus regarding the pes planus definition, the dearth of investigation into pain/complications and the few existing studies, more research is needed to determine a relation between children's body weight, pes planus and associated effects on pain and function.

In silico optimization of phase-change materials for digital memories: a survey of first-row transition-metal dopants for Ge2Sb2Te5.

Phase-change materials are the alloys at the heart of an emerging class of next-generation, non-volatile digital memory technologies. However, the widely studied Ge-Sb-Te system possesses several undesirable properties, and enhancing its properties, e.g. by doping, is an area of active research. Various first-row transition-metal dopants have been shown to impart useful property enhancements, but a systematic study of the entire period has yet to be undertaken, and little has been done to investigate their interaction with the host material at the atomic level. We have carried out first-principles computer simulations of the complete phase-change cycle in Ge2Sb2Te5 doped with each of the ten first-row transition metals. In this article, we present a comprehensive survey of the electronic, magnetic and optical properties of these doped materials. We discuss in detail their atomic-level structure, and relate the microscopic behaviours of the dopant atoms to their influence on the Ge2Sb2Te5 host. By considering an entire family of similar materials, we identify trends and patterns which might be used to predict suitable dopants for optimizing materials for specific phase-change applications. The computational method employed here is general, and this materials-discovery approach could be applied in the future to study other families of potential dopants for such materials.

Where are family theories in family-based obesity treatment?: conceptualizing the study of families in pediatric weight management.

Family-based approaches to pediatric obesity treatment are considered the 'gold-standard,' and are recommended for facilitating behavior change to improve child weight status and health. If family-based approaches are to be truly rooted in the family, clinicians and researchers must consider family process and function in designing effective interventions. To bring a better understanding of family complexities to family-based treatment, two relevant reviews were conducted and are presented: (1) a review of prominent and established theories of the family that may provide a more comprehensive and in-depth approach for addressing pediatric obesity; and (2) a systematic review of the literature to identify the use of prominent family theories in pediatric obesity research, which found little use of theories in intervention studies. Overlapping concepts across theories include: families are a system, with interdependence of units; the idea that families are goal-directed and seek balance; and the physical and social environment imposes demands on families. Family-focused theories provide valuable insight into the complexities of families. Increased use of these theories in both research and practice may identify key leverage points in family process and function to prevent the development of or more effectively treat obesity. The field of family studies provides an innovative approach to the difficult problem of pediatric obesity, building on the long-established approach of family-based treatment.

Attrition in paediatric weight management: a review of the literature and new directions.

Paediatric obesity continues to be one of the most important health issues facing children and families today, and there remains a need for effective treatment options. There are a few reports in the literature demonstrating high rates of attrition from paediatric weight management programmes, ranging from 27% to 73%. While some studies show that racial/ethnic minorities, the economically disadvantaged and those with higher levels of obesity are at risk, other studies do not. There is some consistency in reasons given by families for attrition from treatment, most often scheduling issues and programmes not meeting family needs or expectations. This review highlights identified contributors to attrition from paediatric weight management and provides a framework to study this problem, based on models of adherence to paediatric medical regimens.

Complete genome sequence of a multiple drug resistant Salmonella enterica serovar Typhi CT18.

Salmonella enterica serovar Typhi (S. typhi) is the aetiological agent of typhoid fever, a serious invasive bacterial disease of humans with an annual global burden of approximately 16 million cases, leading to 600,000 fatalities. Many S. enterica serovars actively invade the mucosal surface of the intestine but are normally contained in healthy individuals by the local immune defence mechanisms. However, S. typhi has evolved the ability to spread to the deeper tissues of humans, including liver, spleen and bone marrow. Here we have sequenced the 4,809,037-base pair (bp) genome of a S. typhi (CT18) that is resistant to multiple drugs, revealing the presence of hundreds of insertions and deletions compared with the Escherichia coli genome, ranging in size from single genes to large islands. Notably, the genome sequence identifies over two hundred pseudogenes, several corresponding to genes that are known to contribute to virulence in Salmonella typhimurium. This genetic degradation may contribute to the human-restricted host range for S. typhi. CT18 harbours a 218,150-bp multiple-drug-resistance incH1 plasmid (pHCM1), and a 106,516-bp cryptic plasmid (pHCM2), which shows recent common ancestry with a virulence plasmid of Yersinia pestis.

Genome sequence of Yersinia pestis, the causative agent of plague.

The Gram-negative bacterium Yersinia pestis is the causative agent of the systemic invasive infectious disease classically referred to as plague, and has been responsible for three human pandemics: the Justinian plague (sixth to eighth centuries), the Black Death (fourteenth to nineteenth centuries) and modern plague (nineteenth century to the present day). The recent identification of strains resistant to multiple drugs and the potential use of Y. pestis as an agent of biological warfare mean that plague still poses a threat to human health. Here we report the complete genome sequence of Y. pestis strain CO92, consisting of a 4.65-megabase (Mb) chromosome and three plasmids of 96.2 kilobases (kb), 70.3 kb and 9.6 kb. The genome is unusually rich in insertion sequences and displays anomalies in GC base-composition bias, indicating frequent intragenomic recombination. Many genes seem to have been acquired from other bacteria and viruses (including adhesins, secretion systems and insecticidal toxins). The genome contains around 150 pseudogenes, many of which are remnants of a redundant enteropathogenic lifestyle. The evidence of ongoing genome fluidity, expansion and decay suggests Y. pestis is a pathogen that has undergone large-scale genetic flux and provides a unique insight into the ways in which new and highly virulent pathogens evolve.

Community voices: views on the training of future doctors in Birmingham, UK.

The United Kingdom (UK) population is diverse with nearly 6% minority ethnic communities. Both patients and doctors experience difficulties when dealing with someone from a different ethnic group. Medical education has failed to keep pace with the changing needs of the diverse population. We report a project in which 12 established (religious/cultural and specific interest) community groups expressed their views on what future doctors should learn about serving diverse populations. Data were obtained by group discussion and through the media using a structured format. Fifteen themes emerged which were grouped under three broad themes: firstly, the identification by group members of their perception of the 'differences' in social and cultural beliefs and behaviours of their individual community; secondly, the identification of characteristics of a culturally sensitive doctor; and lastly, recommendations for changes in medical training. New teaching has been introduced to the medical curriculum that incorporates the themes raised by the communities and which reflects consciousness raising and communication issues.

Analysis of 41 kb of the DNA sequence from the right arm of chromosome II of Schizosaccharomyces pombe.

We report the complete sequence of cosmid c18A7 (41 046 bp insert), located on the right arm of chromosome II of the Schizosaccharomyces pombe genome. The sequence, which partially overlaps with cosmids SPBC4F6 and SPBC336, contains 16 open reading frames (ORFs) capable of coding for proteins of at least 100 amino acid residues in length (one partial) and one small nucleolar RNA (snoRNA). Four known genes were found: swi10 (encoding a mating-type switching protein also involved in nucleotide excision repair); dim1 (encoding a dimethyladenosine transferase); arf1 (encoding ADP-ribosylation factor 1); and pol3 (cdc6) the partial fragment, encoding the 125 kDa catalytic subunit of the DNA polymerase type B. Six ORFs similar to known proteins were found. They include a transporter of the major facilitator superfamily class, a vacuolar sorting protein, an asparagine synthase, a nuclear protein, a reticulum oxidoreductin and a heat shock protein. Each protein product of the other six ORFs has conserved domains and can be assigned a molecular, but not a biological, function. The sequence has been submitted to the EMBL database under Accession No. AL080287.

Teaching sexual history taking to health care professionals in primary care.

OBJECTIVES: Although it is accepted that history taking is central to correct diagnosis, little work has been undertaken on the development of sexual history taking, particularly in a primary care context where sexual health may not occur to the patient. Embarrassment is recognized as one major problem. This paper reports on a series of teaching interventions designed to help primary health care professionals (doctors and nurses) to identify and deal effectively with sexual health issues in the consultation. METHODS: 141 participants took part in nine different courses, with 114 returning evaluations. All courses involved tutorial teaching on clinical and ethicolegal issues and role play with trained professional role-players; some involved video-based dramatizations to particularize principles in context. During role play sessions, which were followed by detailed, contextualized feedback, clinical issues, attitudinal issues (e.g. articulating a sense of personal embarrassment, and the risk of stereotyping), and ethicolegal issues were all discussed, as were examples of words and phrases which participants were invited to try out. OUTCOMES: The overall quality of the courses was rated by participants, on average, at 89.95 (maximum 100), and the relevance of the topic at 91.40. Free text comments centred on the power of the training as a consciousness raiser, on the need to alter communication strategies, the need to change existing clinical practice and the value of role play as a methodology. Interactive courses on sexual health are highly acceptable to participants.